DNA-related processes are regulated by the chromatin environment, in part through non-covalent modifications of histones, the chromatin building blocks. That histone modifications correlate with active transcription is well established. In contrast, little is known about the chromatin dynamics during changes in gene expression or DNA replication. We profiled ten histone modifications during and after S phase at high time resolution, and found that modification dynamics is well explained by DNA replication but not by changes in expression. Modifications followed replication at varying delays, which depended on gene expression and promoter structure. Notably, H3K9 acetylation precedes replication. This effect depends on Rtt109, but not on Gcn5 which we show regulates expression-related H3K9ac. We suggest that H3K9ac is triggered by the super-helical stress preceding the replication fork and may serve to prevent inhibition of gene expression. Our results provide new insights into the interplay between histone modifications, gene expression and DNA replication.
